- Terminal-Selective Functionalization of Alkyl Chains by Regioconvergent Cross-Coupling
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Hydrocarbons are still the most important precursors of functionalized organic molecules, which has stirred interest in the discovery of new C?H bond functionalization methods. We describe herein a new step-economical approach that enables C?C bonds to be constructed at the terminal position of linear alkanes. First, we show that secondary alkyl bromides can undergo in situ conversion into alkyl zinc bromides and regioconvergent Negishi coupling with aryl or alkenyl triflates. The use of a suitable phosphine ligand favoring Pd migration enabled the selective formation of the linear cross-coupling product. Subsequently, mixtures of secondary alkyl bromides were prepared from linear alkanes by standard bromination, and regioconvergent cross-coupling then provided access to the corresponding linear arylation product in only two steps.
- Dupuy, Stéphanie,Zhang, Ke-Feng,Goutierre, Anne-Sophie,Baudoin, Olivier
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supporting information
p. 14793 - 14797
(2016/11/23)
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- Development of novel EDG3 antagonists using a 3D database search and their structure-activity relationships
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Sphingosine-1-phosphate (S1P) is an intracellular second messenger and an extracellular mediator through endothelial differentiation gene (EDG) receptors, which are a novel class of G-protein-coupled receptors. Although EDG has attracted much attention because of its various roles, no selective agonists or antagonists have yet been developed. This could account for the delay in clarifying the physiological roles of members of the EDG family. Because precise structural information on EDG receptors is not yet available, pharmacophore models were generated based on structural information for S1P using the rational drug design software Catalyst. Novel antagonists, 2-alkylthiazolidine-4-carboxylic acids, were retrieved from a three-dimensional database search using the pharmacophore models, and these showed activity for EDG3. On the basis of their nonphosphoric acid structure, more potent antagonists, 2-(m- or p-heptylphenyl)thiazolidine-4-carboxylic acid, were developed.
- Koide, Yuuki,Hasegawa, Takeshi,Takahashi, Atsuo,Endo, Akira,Mochizuki, Naoki,Nakagawa, Masako,Nishida, Atsushi
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p. 4629 - 4638
(2007/10/03)
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